COOPERATIVE EXTENSION UNIVERSITY OF CALIFORNIA DAVIS
ENVIRONMENTAL TOXICOLOGY NEWSLETTER

Vol 13 No 3 September 1993

INTRODUCTION

This issue begins with two articles about the hazards of traditional home remedies to children. Lead has been known to be a problem for some traditional remedies for more than a decade, however it appears to still be the cause of childhood poisonings. Accidental ingestion of another remedy, which did not contain the herb indicated by the label, emphasizes one big difficulty with unregulated substances used medicinally; lack of quality control. We have included two short articles about the hantavirus in this issue. Even though it is not a toxicological problem, we have received many calls about it, and there is widespread interest in these infections (probably due to a mortality rate >50%). Also included is a brief review of a Canadian study of 2,4-D exposure from turf application. This is a particularly interesting study because it did not find any absorption except in subjects who were barefoot and wearing shorts and who contacted the turf one hour after application. The recommendation which follows from this study is; stay off the grass for 24 hours after application, or wear shoes. At the end of the newsletter we include a compilation of materials which are available to UCCE advisors and specialists for use in their programs. Sandy Ogletree, the Extension Toxicology Administrative Assistant, has also put together a detailed list of topics covered in all of the Environmental Toxicology Newsletters from 1980 to present.

LEAD POISONING ASSOCIATED WITH USE OF TRADITIONAL ETHNIC REMEDIES -- CALIFORNIA, 1991-1992

Exposure to lead-based paint is the leading cause of high-dose lead exposure among children in the United States. However, previous reports have documented childhood lead poisoning related to the use of traditional ethnic remedies, and such exposures may not be considered routinely. This article describes a case report of lead poisoning resulting from use of a traditional ethnic remedy and summarizes the identification of this problem as a result of lead poisoning surveillance in California from December 1991 through December 1992.

Case Report

In March 1992, a 2-year-old boy of Mexican origin was tested for lead poisoning as part of a routine well-child examination in Los Angeles. His blood lead level (BLL) was 83 ug/dL, a level classified by the Centers for Disease Control (CDC) as a medical emergency. The child had no apparent clinical manifestations, and his mother was unaware of obvious sources of lead exposure, including traditional ethnic remedies. However, when the term "greta" (a traditional Mexican remedy employed as a laxative) was used in the interview, the mother acknowledged giving the boy this remedy regularly since he was 8 months of age.

Analysis of Surveillance in California

From December 1, 1991, through December 31, 1992, the California Department of Health Services received reports of 40 cases of BLLs >20 ug/dL in children who had received traditional ethnic remedies. BLLs ranged from 20 ug/dL to 86 ug/dL (median: 33 ug/dL). Ages of the children ranged from 8 months to 5 years (median: 2 years). Of the 36 children for whom sex was known, 27 (75%) were male. Of the 37 children with known surnames, 33 (89%) had Hispanic surnames; two (5%), Asian/Pacific Islander; and two (5%), Asian Indian. More than half (57%) of the children resided in southern California, 24% in the San Francisco Bay area, 12% in the Central Valley, and 7% in rural northern California. By comparison, 72% of all publicly funded childhood blood lead screening tests were performed in southern California, 11% in the Bay area, 14% in the Central Valley, and 3% in rural northern California.

Of the 40 children, 24 were asymptomatic; of these, five had BLLs >50 ug/dL, including two in whom the BLL was >80 ug/dL. For 36 of the 40 cases, the traditional remedies reported were the Hispanic remedies azarcon or greta. Other remedies were paylooah (Southeast Asia, two cases), surma (India, one case), and an unnamed ayurvedic (a system of medicine practiced in India using herbs, oils, etc. for treating disease) substance from Tibet (one case). In many cases, family members initially denied remedy use but reported such use during subsequent case follow-up efforts.

Results of environmental investigations were available for 18 of the 40 children. For seven of these children, investigators identified other environmental lead sources at levels that probably contributed to the exposures. These sources included paint (levels >5000 parts per million [ppm], maximum of 150,000 ppm), bean pots or other large holloware (leaching >1 ppm lead), and soil (lead levels above 500 ppm).

Editorial Note: In the report, more than half the children had clinically inapparent cases of lead poisoning; nearly all were identified as a result of routine screening of children that had been initiated in California in late November 1991. All of these children had BLLs that substantially exceeded the CDC level of concern (10 ug/dL). Investigation of these cases resulted in the recognition that traditional ethnic medicines may be used not only to treat abdominal complaints but also to prevent illness.

Although neurobehavioral development may be impaired in children with BLLs as low as 10 ug/dL, overt manifestations of lead poisoning generally may not be detected until BLLs exceed 50 ug/dL. Frank encephalopathy (severe neurological disorder) has been noted in children with levels as low as 70 ug/dL. The detection of BLLs >50 ug/dL in children who were asymptomatic underscores the role of screening as a means for identifying children with dangerous levels of lead exposure.

The reluctance of family members to report the use of traditional ethnic medicines during initial interviews may reflect factors such as uncertainty about the legality of using such medicines, belief in the effectiveness of these remedies, and concerns regarding responsibility for the child's elevated BLL. In addition, because some persons may not consider these substances to be "remedies" or "medicines," health-care providers and public health investigators should ask about the use of these substances by their common names.

The finding of additional sources of lead probably contributing to exposure in seven cases underscores the importance of searching for all possible sources of lead exposure in cases of lead poisoning. Health professionals serving communities with high-risk populations should be aware of these high-dose sources of lead exposure. Education of parents about the risks of administering lead-containing substances to their children should be a routine part of health-care maintenance in such high-risk groups or settings.

REF: Morbidity and Mortality Weekly Report, 42(27), July 16, 1993.

JIN BU HUAN TOXICITY IN CHILDREN -- COLORADO, 1993

The consumption of traditional ethnic remedies can have adverse health effects, especially among children. Life-threatening bradycardia (slow heart rate) with rapid onset and central nervous system (CNS) and respiratory depression developed in three unrelated children in Colorado during 1993 following ingestion of Jin Bu Huan tablets, a Chinese herbal medicine used for relieving pain. This report summarizes the investigations of these cases.

Patient 1. A 13-month old boy was lethargic and breathing abnormally when found by his mother approximately 20 minutes after he ingested approximately 60 Jin Bu Huan tablets. The child exhibited CNS depression and was responsive only to painful stimuli. In the emergency department, he was lethargic, with hypotonia, and transient bradycardia. An extensive toxicologic screen was negative. He was treated with activated charcoal through an orogastric tube. He became more alert during the next 10 hours until his physical examination and mental status were completely normal. Follow-up indicated no permanent sequelae.

Patient 2. A 2 1/2-year-old girl was lethargic and breathing abnormally when found by her mother 30-60 minutes after she ingested approximately 17 Jin Bu Huan tablets. Paramedics found the child unresponsive with respiratory depression. An acute episode of bradycardia was successfully treated with atropine. Initial examination in the emergency department indicated miotic pupils, CNS depression, and a disconjugate gaze. The patient's respiratory rate diminished, requiring intubation within 20 minutes after arrival to the emergency department. During the next hour, the child's condition improved, and during an episode of vomiting, she extubated herself. Gastrointestinal decontamination treatment included performing gastric lavage and administering activated charcoal and a cathartic. She remained intermittently lethargic with diffuse muscle weakness until approximately 8 hours following ingestion. Urine and serum toxicologic screens were negative for more than 30 substances. She was discharged the following day after a complete recovery. Follow-up indicated no permanent sequelae.

Patient 3. A 23-month old girl was lethargic when found by her parents within 1 hour after she ingested approximately 7 Jin Bu Huan tablets. The child was transported to an emergency department 1 1/4 hours following ingestion. Gastrointestinal decontamination consisted of performing gastric lavage (resulting in recovery of pill fragments) and administering activated charcoal and a cathartic. She was observed in the emergency department until 5 hours following ingestion and was discharged. Follow-up indicated no permanent sequelae.

Follow-up investigation. Analysis of Jin Bu Huan tablets retrieved from the parents of the three children was performed at Colorado State University. The tablets were 36% concentrated weight-by-weight levo-tetrahydro- palmatine (L-THP), a substance present in the plant genus Stephania but not in the genus Polygala -- the plant of origin indicated on the product package insert. Each tablet contained 28.8 mg L-THP; no other plant alkaloids were present in tablets tested from multiple bottles of Jin Bu Huan. As a result of this investigation, Jin Bu Huan anodyne tablets and their active ingredient (L-THP) were entered into the update of an international toxicologic data base.

Editorial Note: Traditional Chinese herbal products are widely available in the United States. However, because they are not marketed as a drug, these products have not been subjected to standard tests for safety and effectiveness. Jin Bu Huan is manufactured in China, and the stated ingredients are Polygla Chinensis L. alkaloid (30%) and starch (70%). The insert accompanying Jin Bu Huan anodyne tablets describes its action to be anodyne (analgesic), sedative, antispasmodic, and hypnotic and states it to be "a particularly good remedy for the patient suffering from insomnia due to pain." In addition, it lists specific medical indications for the product including "gastric ulcer, duodenal ulcer pains, stomachic [sic] neuralgia, pain in shrunken womb after childbirth, nervous insomnia, spasmodic cough, etc." Although this product was sold as a dietary supplement in health food stores, claims on the labeling that the product is for the treatment, prevention, mitigation, or cure of a disease make it subject to regulation as a drug.

The clinical presentations of and findings in the three children described in this report are consistent with those detected in animals exposed to L-THP. In particular, exposure of animals to L-THP results in sedation, analgesia, neuromuscular blockade, and dopamine receptor antagonism. These studies also have documented L-THP to be naloxone resistant with no affinity for opiate receptors. The investigation has not detected evidence of pharmaceutical contamination of this product. However, its potential toxicity may result from a combination of factors, including the extreme potency of L-THP, the misidentification of the plant from which the product was derived, the false and potentially misleading medical claims, the availability of the product, and lack of childproof packaging.

The public health implications associated with the use of herbal products in the United States are potentially great because many persons use such herbs and other unconventional products. For example, a recent study of the prevalence and frequency of use of unconventional therapy in the United States indicated that 3% of adult respondents reported using an herbal medicine during the preceding year. In addition, a study in the United States of dietary supplement advertising indicated that 22% of these products did not list ingredients in their advertisements. The investigation of the three cases in this report does not provide an adequate basis for assessing the health impact of these products; however, the severity of the adverse health effects in these three cases underscores the potential health risks associated with use of these herbal and other botanical products.

To prevent cases of unintentional poisoning associated with herbal and other botanical products, such products should be sold in childproof packaging and kept in childproof containers, and parents should be informed about the potential toxicity of these products. In addition, accurate labeling of the active ingredient is critical to enable prompt and proper medical treatment for unintentional poisoning.

REF: Morbidity and Mortality Weekly Report, 42(33), August 27, 1993.

THE ROLE OF SIGNIFICANT RISK IN OSHA REFORM

Congress is now considering reauthorization of the Occupational Safety and Health Administration (OSHA) in the U.S. Department of Labor. Among other duties, OSHA is responsible for promulgating permissible exposure limits (PELs) for chemicals that will protect workers from material impairment of health. An important issue that has been raised is the proper criteria to be used by OSHA in determining whether workers are exposed to "significant risk," thereby justifying some form of protective regulatory action.

Why Focus on Significant Risks?

Although many workers are exposed to chemicals that have been shown to cause adverse health effects in humans and laboratory animals, OSHA has limited resources to devote to worker-protection rules.

In the current budgetary environment, dramatic increases in federal funding for occupational health are unlikely. Even if Congress were to increase by ten-fold or more the resources dedicated to occupational health and safety, OSHA and NIOSH (National Institute for Occupational Safety and Health) would still not be able to eliminate all risks to workers from the thousands of chemicals used in commerce each day.

The Supreme Court Intervenes

OSHA resisted adopting a significant-risk doctrine throughout the 1970's. In its proposed generic cancer policy of 1977, OSHA took the position that worker exposures to all carcinogens should be reduced to the lowest feasible levels, regardless of the size of the cancer risks faced by workers.

The key turning point was the Supreme Court's decision in the 1980 benzene case. A plurality of the Court, led by Justice John Paul Stevens, rejected OSHA's position, holding that OSHA must establish that an occupational risk is "significant" before taking steps to reduce or eliminate the risk.

In the benzene and cotton-dust cases, the Supreme Court indicated that it was OSHA's responsibility to develop criteria for determining which risks are significant, and then apply these criteria in the context of specific chemicals. The Court recognized that the determination of significant risk requires a mixture of scientific and policy judgments. In discussing the magnitude of worker risks, Justice Stevens opined that a reasonable person might regard a lifetime cancer risk of 1 in 1,000 as significant enough to justify risk-reduction activities yet regard a risk of 1 in 1,000,000,000 as trivial. In a concurring opinion, Justice Powell emphasized that significant risk determinations are ultimately judgmental and should not be regarded as a "mathematical straightjacket."

On the basis of several recent rulemakings, it appears that OSHA has established 1 in 1,000 as a numerical threshold for determining which lifetime cancer risks to workers are significant.

Although OSHA's choice of 1 in 1,000 as a benchmark of significant risk is based on Justice Stevens opinion, it is not clear that the number has been applied in the manner that Stevens intended. While Stevens thought risks greater than 1 in 1,000 could reasonably be regarded as significant, he did not suggest that risks less than 1 in 1,000 are necessarily insignificant. Indeed, his only comment on insignificance was that a risk less than 1 in 1,000,000,000 would surely be regarded as insignificant. Stevens was silent about the significance of risks that fell between 1 in 1,000 and 1 in 1,000,000,000.

Factors Missing from OSHA's Significant-Risk Doctrine

First, judgments about significant risk should reflect concern about the size of the exposed population as well as the magnitude of individual risk. An individual risk level of 1 in 10,000 might reasonably be considered insignificant by OSHA if 10 or fewer workers are exposed, but should certainly be considered significant if 1 million or more workers are exposed.

Second, judgments about significant risk should take into account the severity of the adverse health effect. A risk level of 1 in 1,000 might be regarded as significant when fatal cancer is the expected endpoint. The same probability of subtle immunological dysfunction might not be regarded as significant.

Finally, judgments about significant risk should take account of the scientific quality of the evidence used to calculate risk. For example, a risk level of 1 in 10,000 that is calculated based on observation of working populations might be regarded as significant since the scientific inference is well supported. In contrast, an estimated risk that is ten times larger (1 in 1,000) might be regarded as insignificant if it is based on extrapolation of tumor responses from one strain of rodents that has tested positive only at the maximum tolerated dose, especially if scientists believe that the mechanisms of tumor induction in rodents are unlikely to be applicable to humans. As risk assessment methods improve, it may ultimately be feasible to incorporate these scientific considerations directly into numerical estimates of risk.

REF: Risk in Perspective, 1(3), August 1993.

Emerging Infectious Diseases:
UPDATE: HANTAVIRUS DISEASE -- UNITED STATES, 1993

Since the recognition of acute hantavirus-associated respiratory disease in the United States in May 1993, laboratory evidence of acute hantavirus infection has been confirmed in 30 persons in the southwestern United States; 20 (67%) of these persons have died. Of those 30 persons, 23 resided in the four-corners region (14 in New Mexico, six in Arizona, and three in Colorado). Previously reported cases outside the four-corners states occurred in a Nevada resident and a Texas resident, neither of whom had traveled to the four-corners area, and a resident of another state who had traveled to and presumably was infected in the four-corners area. This report summarizes the other four confirmed cases and describes two cases under investigation; all of these cases occurred outside the four-corners area during July 1992-August 1993.

Nevada. In August 1993, a 51-year-old central Nevada resident rapidly developed bilateral interstitial infiltrates (lungs filling with fluid) and hypoxemia (lack of oxygen) over 12 hours following a 6-day illness characterized initially by fever, myalgia, (muscle pain) nausea, and vomiting, which progressed to coughing and shortness of breath. The patient, who developed high-titered immunoglobulin M (IgM) antibodies to hantavirus, had not traveled to the four-corners area. As of August 11, the patient remained hospitalized.

California. Two cases have been confirmed in California. In the first, in July 1993, a 27-year-old field biologist, who was working on the eastern slope of the California Sierra Nevada mountain range, had acute onset of an illness characterized by 2 days of fever, myalgia, and headache. The patient developed rapidly progressive bilateral interstitial infiltrates and hypoxemia and died the following day. Hantavirus infection was confirmed by IgM serology, PCR, and a positive immunohistochemical stain for hantavirus antigen on lung tissue. The second case was in a 29-year-old ranch worker on the California coast who died of rapidly progressive respiratory failure during September 1992, following 3 days of fever, myalgia, and cough. Recent immunohistochemical staining of preserved autopsy tissues revealed hantavirus antigen. Neither person had recently traveled to the four-corners area.

Editorial Note: Newly recognized cases of acute illness with evidence of hantavirus infection in Louisiana, Nevada, and California, along with previously recognized cases in Nevada and Texas, further demonstrate that hantavirus-associated respiratory illness is not confined to the four-corners area of the southwestern United States. The continued occurrence of hantavirus disease underscores the importance of minimizing risk for exposure to rodents and their excreta.

REF: Morbidity and Mortality Weekly Report, 42(31), August 13, 1993.

HANTAVIRUS INFECTION -- SOUTHWESTERN UNITED STATES: INTERIM RECOMMENDATIONS FOR RISK REDUCTION

The recently recognized hantavirus-associated disease among residents of the southwestern United States and the identification of rodent reservoirs for the virus in the affected areas warrant recommendations to minimize the risk of exposure to rodents for both residents and visitors. These recommendations are based on current understanding of the epidemiologic features of hantavirus infections in the Southwest; they will be periodically evaluated and modified as more information becomes available.

Rodents are the primary reservoir hosts of recognized hantaviruses. Each hantavirus appears to have preferential rodent hosts, but other small mammals can be infected as well. Available data strongly suggest that the deer mouse (Peromyscus maniculatus) is the primary reservoir of the newly recognized hantavirus in the southwestern United States. Serologic evidence of infection has also been found in pinon mice (P. truei), brush mice (P. boylii), and western chipmunks (Tamias spp.). P. maniculatus is highly adaptable and is found in different habitats, including human residences in rural and semirural areas, but generally not in urban centers. Hantaviruses do not cause apparent illness in their reservoir hosts. Infected rodents shed virus in saliva, urine, and feces for many weeks, but the duration and period of maximum infectivity are unknown. The demonstrated presence of infectious virus in saliva of infected rodents and the marked sensitivity of these animals to hantaviruses following inoculation suggests that biting may be an important mode of transmission among rodents.

Human infection may occur when infective saliva or excreta are inhaled as aerosols produced directly from the animal. Persons visiting laboratories where infected rodents were housed have been infected after only a few minutes of exposure to animal holding areas. Transmission may also occur when dried materials contaminated by rodent excreta are disturbed, directly introduced into broken skin, introduced onto the conjunctivae, or, possibly, ingested in contaminated food or water. Persons have also become infected after being bitten by rodents.

Arthropod vectors are not known to have a role in the transmission of hantaviruses. Person-to-person transmission has not been associated with any of the previously identified hantaviruses or with the recent outbreak in the Southwest. Cats and dogs are not known to be reservoir hosts of hantaviruses in the U.S. However, these domestic animals may bring infected rodents into contact with humans.

Known hantavirus infections of humans occur primarily in adults and are associated with domestic, occupational, or leisure activities that bring humans into contact with infected rodents, usually in a rural setting. Patterns of seasonal occurrence differ, depending on the virus, species of rodent host, and patterns of human behavior. Cases have been epidemiologically associated with the following situations:

Hantaviruses have lipid envelopes that are susceptible to most disinfectants (e.g., dilute hypochlorite solutions, detergents, ethyl alcohol [70%], or most general-purpose household disin- fectants). How long these viruses survive after being shed in the environment is uncertain.

The reservoir hosts of the hantavirus in the southwestern United States also act as hosts for the bacterium Yersinia pestis, the etiologic agent of plague. Although fleas and other ectoparasites are not known to play a role in hantavirus epidemiology, rodent fleas transmit plague. Control of rodents without concurrent control of fleas may increase the risk of human plague as the rodent fleas seek an alternative food source.

Eradicating the reservoir hosts of hantaviruses is neither feasible nor desirable. The best currently available approach for disease control and prevention is risk reduction through environmental hygiene practices that deter rodents from colonizing the home and work environment.

The following are some precautions and recommendations to follow:

(Editor's Note: If anyone would like a copy of this article, please give us a call.)

REF: Morbidity and Mortality Weekly Report, 42(RR-11), July 30, 1993.

2,4-D ABSORPTION STUDY

Researchers at the Canadian Centre for Toxicology in Guelph, Ontario, have reported the results of a study designed to test human absorption of 2,4-D from sprayed turf. Total body dose of 2,4-D was determined in 10 volunteers following exposure to sprayed turf 1 hour after application and in 10 volunteers exposed 24 hours after application. The experimental design incorporated various types and amounts of clothing. Each volunteer was exposed to a 2 x 15 meter area of turf for 1 hour, during which the volunteers alternated between walking and sitting or lying on the treated turf. No detectable residues were found in 4-d urine samples supplied by the volunteers except for 3 people who were barefoot and wearing shorts who contacted the turf 1 hour after application. The highest dose was measured in a volunteer who removed his shirt for 30 min of the exposure session. No detectable residues were found in volunteers exposed 24 hours after application.

REF: Veterinary and Human Toxicology, 35(3), June 1993.

PESTICIDE RANKINGS IN WORK DAYS LOST

Aldicarb ranks ninth in number of workdays lost, according to an analysis of California's pesticide monitoring data, an ex-EPA-er told a discussion at the American College of Toxicology's (ACT) 13th annual meeting in San Francisco, October 22-23, 1992. Curt Lunchick, senior chemist, Jellinek, Schwartz & Connolly Inc., Washington DC, said human poisoning incidence data can be important and in some cases are a better predictor than animal data of how pesticides affect public health, although reporting of incidents is spotty. Lunchick analyzed data from California's pesticide monitoring program, which he said revealed that some of the more toxic pesticides were actually implicated in fewer lost work days or hospitalizations for workers. Lunchick said California's program is unique because it requires doctors and other health care providers, including hospitals, to report any pesticide poisoning incident to local health authorities. In turn, the latter authorities report incidents to the state EPA.

He analyzed cholinesterase-inhibiting pesticides, which are known to cause what he called "cluster poisoning" in which more than one person is affected. He said this is not uncommon to see with reentry and spray drift. Analyzing incidents from 1980-1986, Lunchick found that aldicarb ranked ninth in terms of the number of days lost, 3.50. Number l on the list was methamidophos, 8.90 lost work days, followed by diazinon, 6.58; mevinphos, 5.05; metasystox-R, 4.91; and parathion, 4.01. Aldicarb did not rank in the top 5 in an analysis of number of pesticide poisonings/1,000 applications shown by Lunchick. During the period 1982-88, methomyl and parathion led California in total number of agriculture poisonings, 68 and 67, respectively, he said. But when Lunchick "normalized" the incidents/1,000 applications, he found that oxamyl led the list with 1 poisoning/1,000 applications. This was because of the high use of parathion and methomyl in California, he said. However, parathion was second on the list with 0.9 poisonings/1,000, followed by methamidophos, 0.9; carbofuran, 0.7; fenamiphos, 0.6; and malathion, 0.6.

REF: Veterinary and Human Toxicology, 35(3), June 1993.

FLUORIDE DRINKING WATER STANDARD UPHELD BY NRC REPORT

The Environmental Protection Agency's ceiling of 4 ppm for fluoride in drinking water is "appropriate as an interim standard," a National Research Council study panel declared in a report released August 17.

Currently allowed fluoride levels in drinking water do not pose risks of cancer, kidney failure or bone disease, the NRC's Toxicology Subcommittee on Health Effects of Ingested Fluoride concluded. On the other hand, the panel found "inconsistencies in the fluoride toxicity database and gaps in knowledge."

"More research is needed on patterns of fluoride exposure from other sources such as dental products and foods, as well as fluoride's effects on bone strength and tooth enamel," commented Sub-committee Chair Dr. Bernard Wagner, New York University School of Medicine research pathologist, adding, "The current standard should then be reviewed and changed, if necessary, based on the results of that research."

Despite conflicting results from earlier studies and limited data on possible associations between fluoride and risk of hip or other bone fractures, the panel found "no basis" for lowering EPA's current standard. A small percentage of the population will experience moderate or severe staining or pitting of tooth enamel -- known as dental fluorosis -- at current fluoride levels, the report acknowledged, concluding "However, the question of whether to consider dental fluorosis a cosmetic effect or an adverse health effect and the balancing of the health risks and health benefits of fluoride are matters to be determined by regulatory agencies and are beyond the charge or expertise of this committee."

Epidemiological Studies on Cancer Link Recommended

After reviewing more than 50 epidemiological studies examining fluoride in drinking water and human cancer, the NRC panel found "no credible evidence for an association between fluoride in drinking water and the risk of cancer." On the other hand, the studies were "of limited sensitivity," the panel cautioned.

Taking note of a recent National Toxicology Program study that found some evidence of a dose-related increase in osteosarcomas in male rats, the NRC report concluded that "the available animal data are insufficient to demonstrate a carcinogenic effect of fluoride in animals."

While the weight of evidence from both animal and epidemiological studies appears negative, the subcommittee recommended "conducting onr or more carefully designed analytical epidemiological (case-control or cohort) studies to more fully evaluate the relation between fluoride exposure and cancer, especially osteosarcomas, at various sites, including bones and joints. In conducting such studies, it is important thatindividual exposure to fluoride from all sources be determined as accurately as possible."

The NRC panel also examined possible effects of fluoride ingestion on kidney disease, stomach and intestinal problems, infertility and birth defects, and genetic mutations. Noting that the threshold dose in drinking water that produces kidney effects in animals is approximately 50 ppm, the report concluded that "ingestion of fluoride at currently recommended concentrations will not produce kidney toxicity in humans."

Adverse gastrointestinal effects are "not likely" to result from concen- trations of fluoride found in drinking water in the U.S., the panel concluded.

Observing that fluoride concentrations associated with infertility and birth defects in animals are "far higher" than the EPA standard, the panel declared that drinking fluoridated water should have "no adverse effects" on human reproduction.

While fluoride has caused mutations and chromosomal damage in several in vitro tests, the smallest amount that produced these effects was 100 times larger than the average amount found in most U.S. residents, the panel said, suggesting a "large margin of safety" for mutagenicity.

The NRC report, "Health Effects of Ingested Fluoride," is available for $35 plus shipping from the National Academy Press.

REF: Food Chemical News, 35 (26), August 23, 1993.

Environmental Toxicology Extension List of Available "Educational Materials"

UCCE folks who would like a copy of this list as an ASCII file (which would make topic searching very easy) should contact Sandy. It is our hope that by making these materials available, it will be easier for advisors and specialists to cover a wider range of topics.

Slide/Tape Programs Available Through Visual Media

1. Toxicology: The Science of Poisons
2. Toxicity Testing
3. Household Hazardous Waste

Slide Sets Developed for Talks

1. Risk Assessment (Samurai)
2. Food Safety Issues in the 1990's (Samurai)
3. Common Problems in Communicating Concepts of Toxicologic Risk (Samurai)
4. Drug and Pesticide Residues in Food Animals (Samurai)
5. Toxicology of Clean Air (Respiratory Toxicology Issues) (Samurai)
6. The Minor Species Animal Drug Program (Samurai)
7. The Food Animal Residue Avoidance Databank (FARAD) (Samurai)
8. Residues in Foods 1991 (FDA results)
9. California Pesticide Residues in Produce, 1990
10. California Pesticide Residues in Produce, 1991
11. Lead (from Allison Beale's collection)
12. Dose Response Slides
13. Numerous cartoons, etc.

Publications (DANR)

1. Toxicology: The Science of Poisons
2. Plants Poisonous to Livestock in California
3. Livestock Injection Techniques

Other Publications

(EXTOXNET):

Environmental Toxicology Newsletter Issues:

Volume 1 (1980-81)
(1) 2,4-D
(2) Malathion
(3) Toxic Plants I. Cyanide and Nitrate
(4) Toxic Plants II. Pyrrolizidine Alkaloids Volume 2 (1981-82):
(1) Ethylene Dibromide and Methyl Bromide
(2) Risk Assessment and Predictive Toxicology
(3) Toxic Plants III. Lupine
(4) Genetic Toxicology; Rapid In Vitro Test Capabilities; Furadan Toxicity in Pennsylvania Cattle; Amphibian Highs; Use of Lead Tetroxide as a Folk Remedy for Gastrointestinal Illness
(5) Smoking and Cancer; Mushroom Poisoning Among Laotian Refugees - 1981; Unintentional and Intentional Injuries -- U.S.; Phenoxy Herbicide Update

Volume 3 (1982-83):
(1) I. Plants, Pesticides and Other Toxic Chemicals -- Cutaneous Toxicity (Toxic Effects on Skin): Century Plant Dermatitis; Cercarial Dermatitis Among Bathers in California; Don't Get Too Clean, It May Be Dangerous To Your Health
(2) II. Plants, Pesticides and Other Toxic Chemicals -- Current Topics: Silo- Filler's Disease; Oral Contraceptives and Cancer Risk; Formaldehyde; Bonemeal; Rash Illness Associated with Gypsy Moth Caterpillars; Residue Avoidance Program
(3) III. Plants, Pesticides and Other Toxic Chemicals -- Special Edition: Marijuana
(4) IV. Plants, Pesticides and Other Toxic Chemicals -- Current Topics: TMRC (Theoretical Maximum Residue Contribution) and Its Relation to ADI (Acceptable Daily Intake); Carbon Monoxide Intoxication; Cashew Nut Dermatitis; Irrigation Pipe Associated Electrocution Deaths -- Washington; Congenital Malformations; Childhood Lead Poisoning; Cytogenetic Patterns in Persons Living Near Love Canal -- New York

Volume 4 (1983-84):
(1) V. Plants, Pesticides and Other Toxic Chemicals: Pesticide Waste Disposal; Niacin Intoxication -- Bagels; Respiratory Illness -- Carpet Cleaning; Lead Poisoning -- Mexican Folk Remedies; Lead Poisoning -- Hmong Folk Remedies
(2) Common Herbal Teas and The Basis of Their Medicinal Use
(3) Waterfowl Killed by Diazinon Used for Turf Insect Control; Health-Risk Estimates for 2,3,7,8-Tetrachlorodibenzodioxin in Soil; Results of a Pilot Study of Health Effects due to 2,3,7,8- Tetrachlorodibenzodioxin Contamination -- Missouri; Porphyria Cutanea Tarda and Sarcoma in a Worker Exposed to 2,3,7,8- Tetrachlorodibenzodioxin -- Missouri; Leading Work-Related Diseases and Injuries -- U.S.; Poisoning Among Young Children -- U.S.
(4) VI. Plants, Pesticides and Other Toxic Chemicals: Ethyl Alcohol; Caffeine Effects on Blood Flow to the Brain; Datura Poisoning from Hamburger - Canada; Poisoning from Elderberry Juice -- CA; Nonfatal Arsenic Poisoning in Three Hmong Patients -- MN; Fatalities from Occupational Heat Exposure; Ducks Killed by Furadan 5G use in Rice Weevil Control

Volume 5 (1984-85):
(1) VII. Plants, Pesticides and Other Toxic Chemicals: Safe Use of Methyl Bromide for Rodent Burrow Fumigation; Vietnam Veterans' Risks for Fathering Babies with Birth Defects; Organophosphate Insecticide Poisoning among Siblings -- Mississippi; Dermatitis Among Hospital Workers -- Oregon; Harmful Effects from Folk Remedies; Antibiotics in Animal Feeds
(2) VIII. Plants, Pesticides and Other Toxic Chemicals: Pesticide Waste Disposal; Poisonings: Drugs are No. 1 Cause; Outbreak of Diarrhea Linked to Dietetic Candies - New Hampshire; Poultry Giblet-Associated Salmonellosis -- Maine; Botulism from Fresh Foods -- California; Outbreaks of Respiratory Illness Among Employees in Large Office Buildings -- Tennessee, District of Columbia; Carbon Monoxide Poisoning -- South Dakota; Exposure to Ammonia during Removal of Paint from Artificial Turf -- Ohio
(3) IX. Plants, Pesticides and Other Toxic Chemicals: Outbreak of Phototoxic Dermatitis from Limes -- Maryland; Neurologic Findings Among Workers Exposed to Fenthion in a Veterinary Hospital -- Georgia; An Update on 1,3-Dichloropropene; People Don't Buckle Up: Low Risks for Each Trip
(4) Smoking Revisited; Health Hazards Associated with Elevated Levels of Indoor Radon -- Pennsylvania; Acute Hepatic Failure After Occupational Exposure to 2-Nitropropane; Sulfates and Nitrates in Water; Peanut Butter Riskier Than Ever; FARAD (Food Animal Residue Avoidance Databank)

Volume 6 (1986):
(1) Hazardous Agricultural Chemicals in the Environment
(2) Heptachlor
(3) Food and Waterborne Toxicants: The National Pesticide Telecommunications Network (NPTN); Aldicarb Food Poisoning from Contaminated Melons -- California; Ciguatera Fish Poisoning -- Vermont; Restaurant-Associated Scombroid Fish Poisoning -- Alabama, Tennessee; Ammonia Contamination in a Milk Processing Plant -- Wisconsin; Blood Lead Levels Among Office Workers -- New York City; Erosion of Dental Enamel in Swimmers Due to Gas- Chlorinated Swimming Pools; Seat Belt Use -- U.S.; More on PPB (parts per billion) and PPT (parts per trillion)
(4) Another Perspective: Cancer Death Rates in Humans, 1930-1985; The Development of Tests for Carcinogens and Mutagens; Sources of Mutagens in Our Diet; Mutagens Produced by Cellular Metabolism; Carcinogen "Hazard" Comparisons; Relevance of Carcinogenicity Bioassay; Water Pollution, Pesticide Residues, and Cancer
(5) Respiratory and Cutaneous Toxicity Update: Cigarette Smoking among Public High School Students -- Rhode Island; Deaths Due to Chronic Obstructive Pulmonary Disease and Allied Conditions; Decrease in Lung Cancer Incidence among Males -- U.S., 1973-1983; Acute Respiratory Illness Following Occupational Exposure to Wood Chips -- Ohio; Premature Mortality Due to Malignant Neoplasms -- U.S., 1983; Leading Work-Related Diseases and Injuries; Outbreak of Severe Dermatitis among Orange Pickers -- California
(6) Biodegradation of Hazardous Wastes

Volume 7 (1987):
(1) X. Plants, Pesticides and Other Toxic Chemicals: EPA Review of 2,4-D Article by Hoar et al.; Antibiotic Resistance and Human Infections; Occupational Asthma from Inhaled Egg Protein -- Iowa; 1986 Surgeon General's Report: The Health Consequences of Involuntary Smoking; Trends in Mortality from Cirrhosis and Alcoholism -- U.S., 1945-1983; Tularemia -- New Jersey; Communicating Concepts in Toxicology
(2) Symptoms of Irritation Associated with Exposure to Glutaraldehyde -- Colorado; The Prevalence of Cancer -- Connecticut, January 1, 1982; Use of Supplements Containing High- Dose Vitamin A -- New York State, 1983-1984; Vitamin A & Birth Defects; PCB Contamination of Ceiling Tiles in Public Buildings -- New Jersey; Salmonellosis in a School System -- Oklahoma; Outbreak of Occupational Hepatitis -- Connecticut; Suspected Botulism in Cattle; Phenoxy Herbicide Epidemiology Study Negative; Silo Hazards; Liver Toxicity from an Herbal Remedy; Incidence of Cancer & Low Birth Weight in Relation to a Toxic Waste Dump Site in Iowa
(3) XI. Plants, Pesticides and Other Toxic Chemicals: Pesticide and Animal Drug Registration in the U.S. and Australia -- A Comparison; Serum Dioxin in Vietnam-Era Veterans -- Preliminary Report

Volume 8 (1988):
(1) Pesticide Residues in Foods; International Toxicology News; Organophosphate Toxicity Associated with Flea-Dip Products -- California
(2) Grape Pesticides Targeted by United Farm Workers as Threats to Worker and Consumer Safety; Household Hazardous Waste; Veterinary Toxicology Notes: Hazards of New Rodenticides to Pets; Indoor Air Pollution; An Unusual Case of Widespread Chemical Toxicity; Something to Think About -- Playground Related Injuries in Preschool-Aged Children -- U.S., 1983-1987

Volume 9 (1989):
(1) Food Safety Issues: Appreciating Consumer Food Fears; Independent Testing of Foods for Pesticide Residues; Food Safety and Pesticide Enforcement Initiative; Veterinary Toxicology Notes: Drug Storage on Dairy Farms
(2) Food Safety Issues II: NRDC Report and Alar; State Specific Estimates of Smoking-Attributable Mortality and
Years of Potential Life Lost -- U.S., 1985; Smoking-Attributable Mortality, Morbidity, and Economic Costs -- California, 1985; Scombroid Fish Poisoning -- Illinois, South Carolina; Vet Tox Notes: Legal Source of Methylene Blue; Review of Federal Pesticide Proposal
(3)Preliminary Report - (TCDD) 2,3,7,8-Tetrachlorodibenzo-p-dioxin Exposure to Humans -- Seveso, Italy; Leading Major Congenital Malformations Among Minority Groups in the United States, 1981-1986; Endrin Poisoning Associated with Taquito Ingestion -- CA; Lead Poisoning Following Ingestion of Homemade Beverage Stored in a Ceramic Jug -- NY; Veterinary Toxicology Notes: Red Tide Causes Dolphin Deaths
(4) Cadmium and Lead Exposure Associated with Pharmaceuticals Imported from Asia -- Texas; Seizures Temporally Associated with Use of DEET Insect Repellent -- New York and Connecticut; Pesticide Residues and Dietary Risks; Consumers Need to Realize Their Responsibility in Food Safety; Fatalities Attributed to Methane Asphyxia in Manure Waste Pits -- Ohio, Michigan, 1989; Multivitamins Can Cause Toxic Vitamin A Build-Up in Older People; Aldicarb on Watermelons; Pesticide Poisoning Handbook; Staggers in Sheep and Cattle: Humboldt County; Is Hay Treated with Preservatives O.K. for Horses?; New Field Tests for Veterinarians; Pamphlet from the UC Santa Cruz Agroecology Program: "Pesticides in Food: Are You Adequately Informed"
(5) Inadvertent Contamination of Row Crops from Pesticides in Fog; Lead Poisoning in Bridge Demolition Workers -- Massachusetts; Radon Exposure Assessment -- Connecticut; Update: Eosinophilia-Myalgia Syndrome Associated with Ingestion of L-Tryptophan -- U.S.; Crystallized Chemicals Pose Explosion Hazard; Ethylenediamine Dihydroiodide (EDDI); The Regulation of Food Additives in Animal Feeds; Extra-Label Use of Drugs; New Private Sector Support for 4-H Veterinary Science Awards Program

Volume 10 (1990):
(1) Editorial: Can the Environment and Agriculture Coexist?; Agricultural Pesticides: 100% Use Reporting for California
(2) Food Safety Update: Foodborne Disease Outbreaks, 5-Year Summary -- 1983-1987; Pesticide Residues in Food in 1988; Pesticides and Food Safety: Perception vs. Reality; Malathion: Act II; Cancer Classifications for Malathion and PCP; Mass Sociogenic Illness in a Day-Care Center -- Florida; Urban and Agricultural Pesticide Use: How Do They Compare?; Results of Lead Test Field Trials
(3) Society of Toxicology President's Message; Clinical Spectrum of Eosinophilia-Myalgia Syndrome -- California; Eosinophilia-Myalgia Syndrome Update; Transmission of Plasmodium vivax Malaria -- San Diego County, California, 1988 and 1989; Moth-Associated Dermatitis - Cozumel, Mexico; Excerpts from "Should You Jog in the Smog?"; Mercury Exposure from Interior Latex Paint -- Michigan; Elemental Mercury Poisoning in a Household -- Ohio, 1989; Household Hazardous Waste Series #1: Batteries; Regulatory Requirements for Spray Mixes; UC Exemptions from Pesticide Permit Regulations; Veterinarians and the Manufacturing of Drugs; USDA Reports Problems with Sulfa, Gentamicin Residues in Dairy Cows; USDA Reports on Residues in Imported Meat; Tidbits
(4) 1989 CDFA Pesticide Monitoring Results
(5) Book Review - Diet for a Poisoned Planet -- D. Steinman
(6) Veterinary Notes -- Cattle; Analysis of L-Tryptophan for the Etiology of Eosinophilia-Myalgia Syndrome; Ames Assails Animal Tests, Calls for Rethinking Their Utility; OMB Blasts Use of Conservatisms in Risk Assessments; Risk Assessment Not Well Served by Bioassays, Workshop Told; Carbon Monoxide Levels in Indoor Tractor-Pull Events -- Manitoba, Canada; Continuing Education Requirement for Qualified Applicator Certificate Holders; Cleaning Up Toxics at Home

Volume 11 (1991):
(1) Microorganisms: The Drinking Water Contaminants of the '90's?; Nitrates
(2) A "New" Source of Lead; Cancer Mortality in Workers Exposed to 2,3,7,8-Tetrachlorodibenzo-p-dioxin; Darn Government Regulations Get in the Way; Multistate Outbreak of Poisonings Associated with Illicit Use of Gamma Hydroxy Butyrate; Animal Model Found for L-Tryptophan-Linked EMS; NCI-er Says Evidence Links Vitamin C to Cancer Prevention; FDA/APHIS Find Low Pesticide Residues in Processed Foods; Absorption of Sulfamethazine Residues in Meat; Clenbuterol Cause of Spanish Food Poisonings; Moldy Corn Poisoning in California; Update on Criminal Contempt Case; FDA Revises Policy on Aflatoxin from Peanuts in Feed; Of Painkillers & Pets-Forethought & Care Would Make Accidents Rare
(3) Fatal Pediatric Poisoning from Leaded Paint -- Wisconsin, 1990; Fatal Carbon Monoxide Poisoning in a Camper-Truck -- Georgia; Paralytic Shellfish Poisoning -- Massachusetts and Alaska, 1990; Pool Chemical Safety; Pesticide Levels in House Dust Higher Than in Soil, ACS Told; Toxic Air Pollutants and Noncancer Health Risks -- U.S.; Fluoride in Drinking Water; EPA Issue Update -- Questions & Answers; Aldicarb (Temik) Use on Bananas Voluntarily Withdrawn; Chlorination of Animal Drinking Water; No Animal Drug Residues in Milk Found by FDA (4) Eosinophilia-Myalgia Syndrome: Follow-up Survey of Patients -- NY, 1990-91; Acute and Chronic Poisoning from Residential Exposures to Elemental Mercury -- MI, 1989-1990; Multistate Outbreak of Salmonella poona Infections -- U.S. and Canada, 1991; "Roundup" Herbicide Found Relatively Benign; FDA's Computer Food Safety Network Goes "On-Line"; Chopped Newspaper Bedding; Drought-Related Poisoning Hazards in Livestock; Illegal Use of Clenbuterol in Food Animals; Food Animals -- Bovine
(5) Chlorine Gas Toxicity from Mixture of Bleach with Other Cleaning Products -- CA; Childhood Cancers -- NJ, 1979-1985; Cigarette Smoking Among Adults -- U.S., 1988; Cigarette Smoking Among Youth -- U.S., 1989; Update on Pesticides and Ground Water Contamination Regulations; Plant Toxicants in Milk; Nitrofuran Approval Withdrawn; Gentian Violet Policy Withdrawn; FDA's View on Animal Testing Bills

Volume 12 (1992):
(1) Food Quality; A Voice From the Past; Lead; Toxicological Tidbits; Consumer Confidence in Food Safety is Returning; Behavioral Risk Factor Survey of Vietnamese -- CA, 1991; Pesticide Illnesses Drop in California Workers
(2) Land Disposal of Sewage Sludge; MSG Update; Blood Lead Levels Among Children in High-Risk Areas -- CA, 1987-1990; Update on Nitrofurans; Waste Management Materials
(3) Current Research Programs in the Environmental Toxicology Department at UCD
(4) Risk and the Receding Zero; Bacteria Used to Breakdown Parathion and 2,4-D; Surveillance of Children's Blood Lead Levels -- U.S., 1991; National Childhood Lead Poisoning Prevention Conference; Elevated Blood Levels-Adults; Ultrasonic and Subsonic Pest Control Devices; Bovine Somatotropin (BST); Ethanol and Foodborne Disease; Alcohol Involvement in Fatal Motor-vehicle Accidents; Hair Dyes; Aquaculture Drug Use; Plants and Dermatitis; Waste Management; Aspartame Allergy; Spina Bifida Incidence in the U.S., 1983-1990; Prostate Cancer Trends in the U.S., 1980-1988; FDA Pesticide Program Residue Monitoring Program, 1991
(5) Carcinogens and Carcinogenicity; American Chemical Society Meeting; Deja Vu All Over Again; Cost of Food Safety; Folic Acid to Reduce Birth Defects; Eosinophilia Myalgia Syndrome (EMS) Update; Trihalomethanes and Soft Drinks; Ban Oxygen from House and Senate Cafeterias?; Organic Certification Board Held Public Meeting; 1991 USDA-FSIS Residue Data; Chaparral-Induced Toxic Hepatitis; Pesticide Illness and Work Days Lost; Caffeine Dependence; Caffeine Dependence?; MSG Study; Lead Ingestion and Ceramic Glazes; Lead Hotline; Lead Shot is Not Solid Waste; Food Allergies Loom in Public Eye; Patulin in Apple Juice; BST Approval

Volume 13 (1993):
(1) 2,4-D Absorption Study; Unintentional Carbon Monoxide Poisoning Following a Winter Storm; Toddler Deaths Resulting from Ingestion of Iron Supplements; Acute Respiratory Illness Linked to Aerosol Leather Conditioner; Coccidioidomycosis -- U.S., 1991-92; Exposure of Persons >4 yrs to Tobacco Smoke -- U.S., 1988-91; Years of Potential Life Lost Before Age 65, by Race, Hispanic Origin, and Sex -- U.S., 1986-88; Adult Blood Lead Epidemiology and Surveillance -- U.S., 1992; Isolation of Vibrio cholerae O1 from Oysters -- Mobile Bay, 1991-92; Foodborne Outbreak of Escherichia coli O157:H7 Infections from Hamburgers -- Western U.S. 1993; Environmental Tobacco Smoke; Blood Lead Standards; Food Safety Notes; Oil Disease; Chaparral Herbal Products; Pesticides in the Diet of Infants and Children; Nitrosamines in Beer; Hydrogen Cyanide in Food?; Pesticides and Food; Kitchen Danger: Exploding Eggs; Don't Spray that Weed -- Eat It!; House Dust Higher in Pesticides than Outside Soil; Issues Papers; Toxicology Literature; E. Coli O157:H7 Food Poisoning; Gossypol: Safety and Residue Concerns; Ionophore Toxicity
(2) Optimal Use of "Toxic Chemicals"; Chinese Patent Medicines: Mercury; Methemoglobinemia in an Infant -- WI, 1992; Bicycle Helmet Promotion Programs; Ciguatera Fish Poisoning -- FL, 1991; Lead Intoxication Associated with Chewing Plastic Wire Coating; Lead Poisoning in Bridge Demolition Workers; Topics in Minority Health; Too Many Cooks Spoil the Stew; 2,4-D Cancer Link "Weakly Suggestive"; Lyme Disease; Economic Impact of Motor-Vehicle Crashes -- U.S., 1990; Warnings on Interaction Between Air Bags and Rear-Facing Child Restraints; Milk Quality Assurance; Salinomycin Toxicosis in Pigs; Moldy Sweet Potatoes; Question Link Between Human Lung Cancer and Pet Bird Exposure

Video Library

1. Cleaning Up Toxics At Home (30 min)
2. Cleaning Up Toxics In Business (25 min)
3. Basic Toxicology & Risk Assessment (Craigmill & Winter)
4. Indoor Air Pollution - The Invisible Enemy (30 min)
5. Pesticide Residues in Food (60 min)
6. How Safe Is Your Food?
7. Food Safety In Focus
8. The Toxics Initiative: Where Do We Go From Here?
9. Environmental Reporting: Getting the Story Right - CA Prop 65
10. Toxic Trials
11. Alternatives to Chemical Use: Animal Products (28 min)
12. Alternatives to Chemical Use: Plant Products (26 min)
13. Alternatives to Chemical Use: Post Harvest Handling & Processing (35 min)
14. Sources of Chemicals in the Human Food Chain (32)
15. Regulating Chemicals: A Public Policy Quandary
16. Inside-Outside Pesticides (15 min)
17. Frontline: In Our Children's Food (1993)
18. The Invisible Diet
19. Pesticides in Forestry Toxicology: Behavior of Pesticides in a Forest Environment (32 min)
20. Protecting Groundwater: A Guide for the Pesticide User - UCCE
21. Pesticides (CNN, 30 min)
22. Fields of Fear (1985)
23. What's Killing Calvert City (Nova-Frontline)
24. The Toxics Release Inventory: Meeting the Challenge (USEPA)
25. Home Toxics Quiz (30 min)
26. Big Green (30 min)
27. Training Greenhouse Workers to Handle Pesticides Safety (16 min)
28. Farm Workers: Pesticides (1985, Los Angeles)

Computer Programs of Interest

Arthur L. Craigmill, Ph.D.
Environmental Toxicology
University of California
Davis, CA 95616-8588
(916)752-2936 FAX: 752-0903
Email: alcraigmill@ucdavis.edu